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Abstract
Background & aims: Few studies have been conducted to compare the efficacies of stereotactic body radiation therapy (SBRT) and radiofrequency ablation (RFA). Thus, in this multinational study, we compared the effectiveness of SBRT and RFA in patients with unresectable HCC.

Methods: The retrospective study cohort included 2,064 patients treated in 7 hospitals: 1,568 and 496 in the RFA and SBRT groups, respectively. More than half of the patients (56.5%) developed recurrent tumors, mainly after transarterial chemoembolization (44.8%). Propensity score matching was performed to adjust for clinical factors (n = 313 in each group).

Results: At baseline, the SBRT group had unfavorable clinical features compared to the RFA group, including BCLC stage (B-C 65% vs. 16%), tumor size (median 3.0 cm vs. 1.9 cm), and frequent history of liver-directed treatment (81% vs. 49%, all p <0.001). With a median follow-up of 27.7 months, the 3-year cumulative local recurrence rates in the SBRT and RFA groups were 21.2% and 27.9%, respectively (p <0.001). After adjusting for clinical factors, SBRT was related to a significantly lower risk of local recurrence than RFA in both the entire (hazard ratio [HR] 0.45, p <0.001) and matched (HR 0.36, p <0.001) cohorts. In subgroup analysis, SBRT was associated with superior local control in small tumors (≤3 cm) irrespective of location, large tumors located in the subphrenic region, and those that progressed after transarterial chemoembolization. Acute grade ≥3 toxicities occurred in 1.6% and 2.6% of the SBRT and RFA patients, respectively (p = 0.268).

Conclusions: SBRT could be an effective alternative to RFA for unresectable HCC, particularly for larger tumors (>3 cm) in a subphrenic location and tumors that have progressed after transarterial chemoembolization.

Lay summary: It is currently not known what the best treatment option is for patients with unresectable hepatocellular carcinoma. Here, we show that stereotactic body radiation therapy provides better local control than radiofrequency ablation, with comparable toxicities. Stereotactic body radiation therapy appears to be an effective alternative to radiofrequency ablation that should be considered when there is a higher risk of local recurrence or toxicity after radiofrequency ablation.

Affiliations

Nalee Kim  1 , Jason Cheng  2 , Inkyung Jung  3 , Ja Der Liang  4 , Yu Lueng Shih  5 , Wen-Yen Huang  6 , Tomoki Kimura  7 , Victor H F Lee  8 , Zhao Chong Zeng  9 , Ren Zhenggan  10 , Chul Seung Kay  11 , Seok Jae Heo  3 , Jong Yoon Won  12 , Jinsil Seong  13
1 Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Republic of Korea.
2 Department of Radiation Oncology, National Taiwan University Hospital, Taiwan.
3 Division of Biostatistics, Department of Biomedical Systems Informatics, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea.
4 Department of Internal Medicine, National Taiwan University Hospital, Taiwan.
5 Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taiwan.
6 Department of Radiation Oncology, Tri-Service General Hospital, National Defense Medical Center, Taiwan.
7 Department of Radiation Oncology, Hiroshima University Hospital, Japan.
8 Department of Radiation Oncology, The University of Hong Kong, Hong Kong.
9 Department of Radiation Oncology, Zhongshan Hospital, Fudan University, China.
10 Department of Medical Hepatology, Zhongshan Hospital, Fudan University, China.
11 Department of Radiation Oncology, Incheon St. Mary Hospital, Republic of Korea.
12 Department of Interventional Radiology, Yonsei Cancer Center, Yonsei University College of Medicine, Republic of Korea.
13 Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Republic of Korea. Electronic address: jsseong@yuhs.ac.